1. Chromosomes and Gene Expression
Download icon

Chromosome-wide mechanisms to decouple gene expression from gene dose during sex-chromosome evolution

  1. Bayly S Wheeler
  2. Erika Anderson
  3. Christian Frøkjær-Jensen
  4. Qian Bian
  5. Erik Jorgensen
  6. Barbara J Meyer  Is a corresponding author
  1. Rhodes College, United States
  2. Howard Hughes Medical Institute, University of California, Berkeley, United States
  3. Stanford University, United States
  4. Howard Hughes Medical Institute, University of Utah, United States
Research Article
  • Cited 12
  • Views 1,806
  • Annotations
Cite this article as: eLife 2016;5:e17365 doi: 10.7554/eLife.17365

Abstract

Changes in chromosome number impair fitness by disrupting the balance of gene expression. Here we analyze mechanisms to compensate for changes in gene dose that accompanied the evolution of sex chromosomes from autosomes. Using single-copy transgenes integrated throughout the Caenorhabditis elegans genome, we show that expression of all X-linked transgenes is balanced between XX hermaphrodites and XO males. However, proximity of a dosage compensation complex (DCC) binding site (rex site) is neither necessary to repress X-linked transgenes nor sufficient to repress transgenes on autosomes. Thus, X is broadly permissive for dosage compensation, and the DCC acts via a chromosome-wide mechanism to balance transcription between sexes. In contrast, no analogous X-chromosome-wide mechanism balances transcription between X and autosomes: expression of compensated hermaphrodite X-linked transgenes is half that of autosomal transgenes. Furthermore, our results argue against an X-chromosome dosage compensation model contingent upon rex-directed positioning of X relative to the nuclear periphery.

Article and author information

Author details

  1. Bayly S Wheeler

    Department of Biology, Rhodes College, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Erika Anderson

    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Christian Frøkjær-Jensen

    Department of Pathology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Qian Bian

    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Erik Jorgensen

    Department of Biology, Howard Hughes Medical Institute, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Barbara J Meyer

    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    For correspondence
    bjmeyer@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6530-4588

Funding

National Institutes of Health (1R01 GM030702)

  • Barbara J Meyer

Howard Hughes Medical Institute

  • Barbara J Meyer

National Institutes of Health (1F32 GM100647)

  • Bayly S Wheeler

Howard Hughes Medical Institute

  • Christian Frøkjær-Jensen

National Institutes of Health (1R01 GM095817)

  • Erik Jorgensen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Edith Heard, Institut Curie, France

Publication history

  1. Received: April 29, 2016
  2. Accepted: August 29, 2016
  3. Accepted Manuscript published: August 30, 2016 (version 1)
  4. Accepted Manuscript updated: September 1, 2016 (version 2)
  5. Version of Record published: October 3, 2016 (version 3)

Copyright

© 2016, Wheeler et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,806
    Page views
  • 365
    Downloads
  • 12
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Chromosomes and Gene Expression
    Nina Kirstein et al.
    Research Article

    Eukaryotic DNA replication initiates during S phase from origins that have been licensed in the preceding G1 phase. Here, we compare ChIP-seq profiles of the licensing factors Orc2, Orc3, Mcm3, and Mcm7 with gene expression, replication timing and fork directionality profiles obtained by RNA-seq, Repli-seq and OK-seq. ORC and MCM are significantly and homogeneously depleted from transcribed genes, enriched at gene promoters, and more abundant in early- than in late-replicating domains. Surprisingly, after controlling these variables, no difference in ORC/MCM density is detected between initiation zones, termination zones, unidirectionally replicating and randomly replicating regions. Therefore, ORC/MCM density correlates with replication timing but does not solely regulate the probability of replication initiation. Interestingly, H4K20me3, a histone modification proposed to facilitate late origin licensing, was enriched in late replicating initiation zones and gene deserts of stochastic replication fork direction. We discuss potential mechanisms specifying when and where replication initiates in human cells.

    1. Chromosomes and Gene Expression
    2. Computational and Systems Biology
    Anna Nagy-Staron et al.
    Research Article

    Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions, such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks remains a major challenge. Here, we use a well-defined synthetic gene regulatory network to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one gene regulatory network with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual transcriptional units, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of gene regulatory networks.